The present invention relates to the field of medical diagnostics and, more specifically, to an improved substrate and indicator system that are useful, for example, for the diagnosis of medical conditions by identification of vaginal secretions.
Many bodily fluids can be readily identified by chemical properties such as pH One exceptionally useful method of determining the pH of a liquid sample is through the use of an indicator, a chemical compound or combination of compounds, that has a pH dependent color. Well known examples include tea and wine. General details and descriptions of some indicators can be found, for example, in xe2x80x9cIndicatorsxe2x80x9d, E. Bishop, Pergamon Press, 1972, chapter 3, which is incorporated by reference for all purposes as if fully set forth herein.
Often an indicator is attached to a solid substrate such as paper A sample of a liquid of which the pH needs to be determined is applied to the substrate. The pH of the liquid is determined by determining the color of the indicator present on the substrate. Depending on how the indicator is attached to the substrate, application of the liquid sample may cause the indicator to leach out of the substrate. Since in many applications indicator leaching is undesirable, the indicator is often substantially immobilized on the substrate. One use wherein pH sensitive indicators are immobilized on a substrate is in medical diagnostics, specifically when the indicator is incorporated in a swab, gauze, panty shields, hygienic napkin or related product.
Many medical indications can be diagnosed by identifying the nature of a vaginal secretion. One simple method of identifying a vaginal secretion is using pH. A number of devices involving panty shields and related products configured to allow the identification of vaginal secretions by the use of pH indicators have been disclosed. The user wears the device and whenever there is a secretion it is immediately detected and analyzed by the device.
The use of a sanitary napkin configured to identify the pH value associated with vaginosis or bacterial infections has been described in the art, for example in U.S. Pat. Nos. 5,217,444, 5,823,953 and 6,106,461.
U.S. patent application Ser. No. 09/372,571, incorporated by reference for all purposes as if fully set forth herein, discloses an indicator bound to a hydrophilic synthetic membrane substrate. Further U.S. patent application Ser. No. 09/372,571 discloses a device, such as a panty shield with an indicator bound to hydrophilic synthetic membrane substrate inside of an absorbent material.
A general problem of pH indicators in the diagnosis of medical conditions is that of xe2x80x9cfalse positivesxe2x80x9d. Often a secretion gathered from a bodily location can not be identified with absolute certainly by an indicator due to the existence of a plurality of fluids with a similar pH that may be secreted from that bodily location. Thus existing devices are useful, but do not provide a complete solution for identifying a secretion.
A first example illustrating the difficulty in confident identification is the diagnosis of vaginosis. Vaginal secretions of a patient with vaginosis have a pH between 4.7 and 7.0. Since urine of a healthy patient has a pH between 5.0 and 7.0, it is very difficult to diagnose a secretion as arising from vaginosis with a high degree of confidence by just using a pH based indicator test. One solution known, in the art is to sample fluid from within the vagina, where urine is not ordinarily found. This is discomforting and requires a visit to a health-care professional.
A second example is the identification of amniotic fluid leaking from the vagina of a pregnant woman. During pregnancy amniotic sack integrity may be compromised and a small amount of amniotic fluid may leak out through the cervix and from the vagina. If diagnosed as such, measures such as patient rest or sealing of the amniotic sack using biological glue may be prescribed. If not diagnosed the amniotic sack may later rupture causing abortion of the pregnancy, or require hospitalization of the woman and infant. If the infant is born prematurely, death or severe handicap may be a result. Extended hospitalization of the infant in an incubator is often necessary.
Due to the severe consequences of amniotic fluid leakage, pregnant women undergo severe stress and often go to a health-care professional upon secretion of any liquid from the vicinity of the vagina. The health-care professional looks for the presence of amniotic fluid by checking the pH of the vaginal secretions, amniotic fluid having a pH of between 7.0 and 7.5. Since pregnant women often have urinary incontinence and since urine typically has a pH of between 5.0 and 7.0, if only pH is checked, a false positive result may occur, urine being identified as amniotic fluid. Consequently, it is necessary that such a vaginal secretion be examined using a microscope for the presence of a fern-shaped pattern indicative of amniotic fluid.
As the time between the fluid secretion and the arrival at the health-care professional may be long, there is often no evidence of amniotic fluid upon examination. The secretion is mistakenly assumed to be urine, often with tragic consequences. On the other hand, the health-care professional may decide to err on the side of caution, misdiagnosing the secretion of urine as amniotic fluid leading to an unnecessary hospitalization and concomitant patient stress.
In order to increase the confidence in such diagnoses, a number of systems have been disclosed.
In U.S. Pat. No. 6,149,590 a device in the form of a sanitary napkin with a pH indicator configured to identify the presence of amniotic fluid in a vaginal secretion is disclosed. The device further includes a microscope visualizable slide configured to gather a portion of a vaginal secretion. If the indicator shows the pH corresponding to that of amniotic fluid, the user presents a health-care professional with the slide. The health-care professional examines the slide with the help of a microscope for the typical fern-shaped patterns indicative of the presence of amniotic fluid. A disadvantage of this device is that it requires that the patient visit the health-care professional as a result of any secretion of liquid from the vaginal area.
U.S. Pat. No. 5,897,834, incorporated by reference for all purposes as if fully set forth herein, discloses a device useful in a clinical setting for the confident differentiation between urine and vaginal secretions associated with vaginosis or urine and amniotic fluid. The device includes the use of indicators with a negatively charged group immobilized to a solid polymer substrate containing quaternary ammonium groups. Further the device includes a gaseous amine-releasing reagent and an amine indicator. The use of the polymer substrate containing quaternary ammonium groups is disclosed to have an advantage of sharpening the pH dependent color transition. However, these polymer substrates have been found to be less useful in non-clinical settings: the indicated pH of dried out vaginal secretions is low enough to be misdiagnosed as indicating vaginosis. Thus although the device disclosed in U.S. Pat. No. 5,897,834 is useful in a clinical setting where the health care professional applies the vaginal secretion to the device and observes the color change, if integrated in a patient useable device, such as a panty shield, the device gives abundant false positive results.
There is a need for an indicator system that can differentiate between urine and either amniotic fluid or vaginal secretions related to vaginosis. Further, such a system is ideally useable by the patient to lead to greater peace of mind and to minimize unnecessary hospital visits and the accompanying stress, with few false positive results. The characteristics of such an indicator system must not change due to long use or as a result of a wetting/drying cycle.
The above and other objectives are achieved by the use of an indicator system and integration into products of the indicator system of the present invention.
According to the teachings of the present invention there is a device with a substrate to which are attached a first pH indicator in an area or areas (hereinfurther termed xe2x80x9cfirst areasxe2x80x9d), a second pH indicator in an area or areas (hereinfurther termed xe2x80x9csecond areasxe2x80x9d), and a reagent attached to the substrate in the second areas, where substantial color transitions of each of the two indicators occur at a substantially dissimilar pH. A liquid contacting the substrate interacts with the indicators and the reagent. If the liquid has the pH of a fluid that is to be identified, at least part of the first areas undergoes a substantial color change. The liquid may be an interfering fluid with a pH that changes the color of the first indicator. Therefore, the reagent is selected to react with the interfering fluid (for example), changing the pH of the liquid and consequently substantially changing the color of at least part of the second areas. The presence of the second pH indicator acts as a guarantee against false positive results by allowing a colorimetic differentiation of two fluids with a similar pH. According to a feature of the present invention, the first pH indicator changes color at a substantially lower pH than does the second pH indicator. Usually the first areas are distinct from the second areas. The shape of the areas can be anything, including geometrical shapes, icons and words.
According to a feature of the present invention, the device has an absorbent body in contact with the substrate so that fluids absorbed by the absorbent body wet the substrate. According to a further feature of the present invention, fluid absorbed by the absorbent body must first pass through a microporous membrane.
According to a feature of the present invention the first pH indicator and the second pH indicator both have a substantially negatively charged functional group.
There is also provided according to the teachings of the present invention an absorbent body for absorbing vaginal fluids (for example in the shape of a sanitary napkin, a panty shield or a gauze pad) with an absorbent material in contact with a substrate in such a way that the substrate is wet by fluids absorbed by the absorbent material. To the substrate are attached a first pH indicator in a first areas, a second pH indicator in a second areas, and a reagent attached to the substrate in the second areas, where the color transitions of each of the two indicators occur at a substantially dissimilar pH. According to feature of the present invention, the absorbent body includes a means for mounting the absorbent body in such way that it absorbs fluids secreted from the vicinity of the vaginal area of a female.
There is also provided according to the teachings of the present invention a method for providing an indication of the health condition of a person by providing a substrate to which are attached a first pH indicator in a first areas, a second pH indicator in second areas, and a reagent attached to the substrate in the second areas, where the color transitions of each of the two indicators occur at a substantially dissimilar pH. A liquid (such as liquid secreted from the vaginal area) is applied to the substrate and the first and second areas are inspected for a change in color indicative of the health condition of the person. According to a feature of the present invention, the substrate is retained in the vicinity of a vaginal area of the person for an extended period of time such as minutes, hours or even longer.
According to a feature of the present invention, in all cases hereinabove, the reagent is urease.
According to a further feature of the present invention, in all cases hereinabove, the first pH indicator is configured to substantially change color upon contact with amniotic fluid and the second pH indicator is configured to substantially change color upon contact with urine reacting with the reagent.
According to a still further feature of the present invention, in all cases hereinabove, the first pH indicator is configured to substantially change color upon contact with vaginal secretions associated with vaginosis and the second pH indicator is configured to substantially change color upon contact with urine reacting with the reagent.
There is also provided according to the teachings of the present invention a method of attaching an indicator to a substrate. The substrate can be made of many materials including polypropylene membranes, paper or cotton, and can be of many structures including of a membrane, fabric, mesh, gauze, thread, fiber and a sheet. A mixture of pre-formed polymer (such as a cellulose), a plasticizer, a wetting agent, an ion-balance reagent and an indicator (alone or with a reagent such as urease) is prepared. In some cases it is preferable to add a solvent to the mixture. The mixture is applied to a substrate for example by dipping the substrate in the mixture or by spraying or spreading the mixture onto the substrate. The substrate with the applied mixture is allowed to dry. When dry, the indicator is bound to the substrate with the help of the polymer. This method is exceptionally useful when the indicators have a substantially negatively charged functional group such as an acetate or a sulfonate.
There is also provided according to the teachings of the present invention an additional method of attaching an indicator to a substrate, especially a neutral substrate, by applying a surfactant solution to the substrate and letting it dry (preferably under vacuum). Once the surfactant is dry, an indicator solution (or a solution with a reagent, such as urease) is applied to the substrate and allowed to dry (also preferably under vacuum). When the indicator to be attached to the substrate has a substantially negatively charged functional group, a cationic surfactant is preferably used.